AB0184 SENSORY PROFILING IN CLASSICAL EHLERS-DANLOS SYNDROME: EVIDENCE FROM A CASE-CONTROL STUDY REVEALS PAIN CHARACTERISTICS, SENSORY CHANGES AND IMPAIRED PAIN MODULATION
Authors: M. Colman, D. Wille, I. De Wandele, L. Rombaut, A. M. Malfait, M. Meeus, J. Van Oosterwijck, D. Syx, F. Malfait
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The Ehlers-Danlos syndromes (EDS) are a paradigm group of rare heritable connective tissue disorders caused by pathogenic defects in genes involved in biosynthesis, fibrillogenesis, and/or supramolecular organization of collagen fibrils in the extracellular matrix (ECM). Joint hypermobility, skin hyperextensibility, abnormal wound healing and easy bruising are among the cardinal clinical features. The classical EDS type, caused by caused by defects in type V or rarely type I collagen, is the most prevalent genetically elucidated EDS type [1]. (Chronic) pain is highly prevalent in individuals with EDS and is one of the foremost reasons these individuals seek medical attention. There is a high use of analgesics, surgery, and physical therapy but these treatment modalities often bring only modest relief at best, and some are associated with unwanted side effects. Few studies, almost exclusively conducted in the molecularly unexplained hypermobile EDS type, have brought limited evidence for neuropathic pain and decreased intra-epidermal nerve fiber density. Interestingly, functional and structural abnormalities of the nervous system and associated pain-related behaviors have also been described in mouse models of EDS [2]. Comprehensive human studies on pain prevalence and pain mechanisms in molecularly solved EDS types are however currently not available, thereby representing a major gap in the study of pain in EDS. <h3>Objectives</h3> The primary aim of this cross-sectional study was to identify the sensory profile of individuals with cEDS. Secondly, we aimed to identify the pain characteristics and the emotional-cognitive burden in cEDS. <h3>Methods</h3> Nineteen individuals with molecularly confirmed cEDS and 19 healthy matched control were recruited. Sensory profiling included sensitivity to innocuous and noxious stimuli of multiple modalities (electrical, thermal, vibration, touch, pressure) and a parallel and sequential conditioned pain modulation protocol. Moreover, pain characteristics and emotional-cognitive factors that are known to influence pain processing were studied using a set of validated questionnaires (PD-Q, DN4, HADS, HAQ, SF-36, CSI, PVAQ, TAMPA scale). <h3>Results:</h3> The cEDS cohort showed an altered sensory profile. Higher (p=0.04) detection thresholds for vibration stimuli at the lower limb were found indicating the presence of hypoesthesia. Reduced/altered thermal sensitivity was found with significantly more (p&lt;0.001) paradoxical thermal sensations at the lower limb (usually to heat). Lower pain thresholds were found to mechanical (p&lt;0.001) stimuli at both the upper and lower limbs and to cold (p=0.005) stimulation at the lower limb indicating hyperalgesia. Using a parallel conditioned pain paradigm, significantly (p=0.005 and p=0.046) smaller antinociceptive responses were shown in cEDS suggestive of impaired central pain inhibition. <h3>Conclusion</h3> This study represents the first systematic investigation of pain in a genetically defined EDS type. With evidence for sensory changes and impaired pain modulation in cEDS, we provide new insights on the possible role of the ECM in the development and persistence of pain. <h3>References</h3> [1] Malfait <i>et al.</i> Am J Med Genet C Semin Med Genet 2021;187(4):429-445. [2] Malfait <i>et al</i>. Nat. Rev. Dis. Primers 2020;6(1):64. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.